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Myosin IXB gene region and gluten intolerance: linkage to coeliac disease and a putative dermatitis herpetiformis association

¹ Department of Medical Genetics, and Research Program of Molecular Medicine, University of Helsinki, Finland
² Heim Pal Children’s Hospital, Budapest, and University of Debrecen, Hungary
³ Paediatric Research Centre, University of Tampere Medical School and Tampere University Hospital, University of Tampere, Finland
⁴ Faculty of Public Health, Department of Preventive Medicine, University of Debrecen, Debrecen, Hungary
⁵ Faculty of Public Health, Department of Epidemiology and Biostatistics, University of Debrecen, Debrecen, Hungary
⁶ Complex Genetics Section, DBG-Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands
⁷ Genetics Department, University Medical Center Groningen, Groningen, The Netherlands
⁸ Research and Development, Finnish Red Cross Blood Service, Helsinki, Finland
⁹ Karolinska Institutet, Department of Biosciences and Nutrition, Novum, Huddinge, Sweden

Correspondence to:
P Saavalainen, Department of Medical Genetics, Haartman Institute, Biomedicum Helsinki, PO Box 63, FIN-00014 University of Helsinki, Finland; paivi.saavalainen{at}helsinki.fi]

Background: Coeliac disease is caused by dietary gluten, which triggers chronic inflammation of the small intestine in genetically predisposed individuals. In one quarter of the patients the disease manifests in the skin as dermatitis herpetiformis. Recently, a novel candidate gene, myosin IXB on chromosome 19p13, was shown to be associated with coeliac disease in the Dutch and Spanish populations. The same gene has previously been associated with inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis risk, making myosin IXB a potential shared risk factor in these inflammatory disorders.

Methods: In this study, previously reported myosin IXB variants were tested for genetic linkage and association with coeliac disease in 495 Hungarian and Finnish families and in an additional 270 patients and controls.

Results and conclusion: The results show significant linkage (logarithm of odds (LOD) 3.76, p = 0.00002) to 19p13 which supports the presence of a genuine risk factor for coeliac disease in this locus. Myosin IXB variants were not associated with coeliac disease in this study; however, weak evidence of association with dermatitis herpetiformis was found. The association could not explain the strong linkage seen in both phenotypes, indicating that the role of other neighbouring genes in the region cannot be excluded. Therefore, more detailed genetic and functional studies are required to characterise the role of the myosin IXB gene in both coeliac disease and dermatitis herpetiformis.